The purpose of the research proposed in this application is to identify the importance of the coronary and collateral vasculature as modifiers of the natural history of ischemic heart disease and to gain insight into the mechanisms which stimulate vascular development in the dog and pig so that means could be developed to prevent or reduce ischemic injury in man. Knowledge will be obtained as to whether a pressure gradient or regional ischemia is the primary stimulus for vascular proliferation. The second objective of this research is to identify the role of the coronary vasculature in long-term regulation of coronary flow, and to determine how coronary vasculature adapts to physio-pathological stress situations. The third objective is to identify the interrelationship between the coronary and collateral circulation. The experimental model chosen for this research is the animal with gradual coronary occlusion (Ameroid occlusion), rather than acute occlusion. This model more closely resembles the arteriosclerotic process seen in man. Experiments with exercise, anemia, hypertension, and drugs are proposed. Following these long-term experiments, the coronary and collateral vasculature will be assessed utilizing an isolated heart preparation (for optimal control of extrinsic factors) and utilizing new methods for determining coronary and collateral resistances. Histopathological examinations of the hearts in these studies are hoped to establish a correlation between coronary collateralization and infarction.